GENE-GENE INTERACTIONS OF POLYMORPHIC LOCUSES OF LIPID AND CARBOHYDRATE METABOLISM GENES ASSOCIATED WITH THE MYOCARDIAL INFARCTION RISK IN PATIENTS WITH OBESITY

Highlights

Combined interactions of polymorphic loci in lipid and carbohydrate metabolism genes in patients with myocardial infarction) and obesity were studied in the presented research. It was hypothesized that these interactions can explain the individual differences in the risk of cardiometabolic disorders due to modulation of their manifestation.

Aim. To investigate the patterns of gene-gene interactions of polymorphic loci in lipid and carbohydrate metabolism genes in patients with myocardial infarction depending on the presence of comorbid obesity.

Methods. 146 patients with acute myocardial infarction, divided into groups with and without obesity were examined. The control cohort consisted of 300 apparently healthy residents of the region. DNA was isolated from peripheral blood using phenol-chloroform extraction. Genotyping of 12 polymorphic variants in 8 genes involved in the regulation of lipid and carbohydrate metabolism was performed using the TaqMan assay on a ViiA™ 7 analyzer. Gene-gene interaction analysis was performed using MDR v.3.0.2.

Results. In this study, significant associations between the IGF1R gene rs2229765 polymorphism and APOE gene rs7412 polymorphism associated with an increased obesity risk in myocardial infarction patients were identified. Using the MDR assay, key gene-gene interaction models were identified: a four-locus model associated with myocardial infarction risk (rs1137101 LEPR – rs1137100 LEPR – rs1042031 APOB – rs6725189 APOB) and a twelve-locus model associated with obesity risk including all analyzed polymorphic loci. The greatest entropic contributions to myocardial infarction risk were found to be made by APOB gene rs6725189 polymorphism, LEPR gene rs1137100 polymorphism, and LIPC gene rs1800588 polymorphism, while a pronounced synergistic effect was detected for the rs6725189-rs1042031 (APOB) pair. In the obesity risk model, the greatest individual contributions were observed for APOE gene rs7412 polymorphism and IGF1R gene rs2229765 polymorphism, while strong synergistic interactions were observed for pairs including LEPR gene rs1137100 polymorphism.

Conclusion. Assessment of gene-gene interactions revealed that the combined pathogenetic effects of polymorphic loci of lipid and carbohydrate metabolism genes exceed their independent contributions. This finding can be used to assess the genetic risk of myocardial infarction and develop personalized approaches to the prevention and management of patients with cardiometabolic comorbidity.

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